抑制星形胶质细胞半通道可防止扩散抑制过程中的突触传递衰退。

IF 4.3 2区 生物学 Q1 BIOLOGY
Juan E Tichauer, Matías Lira, Waldo Cerpa, Juan A Orellana, Juan C Sáez, Maximiliano Rovegno
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引用次数: 0

摘要

背景:扩散抑制(SD)是一种有趣的现象,其特征是影响神经元和神经胶质细胞的大规模缓慢脑去极化。这种现象具有重复性,会产生新陈代谢超载,从而增加继发性损伤。然而,SD 的启动和传播机制尚不清楚。多种证据表明,半通道持续、不受控制的开放可能参与了包括急性脑损伤在内的多种神经系统疾病的发病和进展。在此,我们探讨了由 connexin-43 (Cx43) 或 pannexin-1 (Panx1) 组成的星形胶质细胞半通道对高 K+刺激诱发脑片 SD 的贡献:结果:局灶性高K+刺激可迅速诱发SD波,这与大脑皮层中Cx43和Panx1半通道活性的增加有关,这分别是通过透光率和染料吸收分析测定的。这些通道的激活主要发生在星形胶质细胞中,但也发生在神经元中。更重要的是,抑制 Cx43 和 Panx1 半通道可完全阻止高 K+诱导的大脑皮层 SD。电生理记录还显示,Cx43和Panx1半通道对SD诱导的大脑皮层和海马突触传递的减少起着关键作用:结论:靶向 Cx43 和 Panx1 半通道可作为一种新的治疗策略,在多种急性脑损伤中预防 SD 的发生和传播。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression.

Background: Spreading depression (SD) is an intriguing phenomenon characterized by massive slow brain depolarizations that affect neurons and glial cells. This phenomenon is repetitive and produces a metabolic overload that increases secondary damage. However, the mechanisms associated with the initiation and propagation of SD are unknown. Multiple lines of evidence indicate that persistent and uncontrolled opening of hemichannels could participate in the pathogenesis and progression of several neurological disorders including acute brain injuries. Here, we explored the contribution of astroglial hemichannels composed of connexin-43 (Cx43) or pannexin-1 (Panx1) to SD evoked by high-K+ stimulation in brain slices.

Results: Focal high-K+ stimulation rapidly evoked a wave of SD linked to increased activity of the Cx43 and Panx1 hemichannels in the brain cortex, as measured by light transmittance and dye uptake analysis, respectively. The activation of these channels occurs mainly in astrocytes but also in neurons. More importantly, the inhibition of both the Cx43 and Panx1 hemichannels completely prevented high K+-induced SD in the brain cortex. Electrophysiological recordings also revealed that Cx43 and Panx1 hemichannels critically contribute to the SD-induced decrease in synaptic transmission in the brain cortex and hippocampus.

Conclusions: Targeting Cx43 and Panx1 hemichannels could serve as a new therapeutic strategy to prevent the initiation and propagation of SD in several acute brain injuries.

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来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
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